Tag: intensive care
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Abstract

Inotropic agents are used to increase myocardial contraction while vasopressors are used to increase vascular tone. They are often used for treatment of patients whose tissue perfusion is insufficient to meet metabolic requirements. Therefore, these agents are usually administered in intensive care units where continuous and invasive monitoring of cardiac function can be applied.

Inotropic agents can be divided into those that increase cAMP levels and those that do not. Adrenergic receptor agonists and phosphodiesterase inhibitors (PDEi) increase cAMP levels and are currently the mainstay of positive inotropic therapy. Levosimendan acts as calcium sensitizer and increases myocardial contraction force without increasing intracellular calcium levels. In addition to existing inotropic agents, new promising inotropes are being developed. These include sarcoplasmic reticulum calcium pump (istaroxime), cardiac myosin activators (omecamtivmecarbil), gene therapy, nitroxyl donors and ryanodine receptor stabilizers.

Current treatments of heart failure are aimed at prolonging survival and not just alleviating symptoms. This review provides a short description of the physiology of myocardial contraction and adrenergic receptors. We also provide a short description of commonly used inotropic agents and vasopressor drugs as well as a short review of agents that are expected are in use in the future.

Inotropes are agents used to increase myocardial contractility, while vasopressors are administered to increase vascular tone(1).Their use ismostly confined to critically ill patients whose hemodynamic impairment is such that tissue perfusion is insufficient to meet metabolic requirements(2). Patients in need of inotropic or vasopressor support are often presented with septic or cardiogenic shock and severe heart failure, and are victims of major trauma or undergoing major surgery.These drugs are therefore administered usually to patients treated in intensive care settings where continuous monitoring of cardiac rhythm, arterial oxygenation, urine output and other invasive hemodynamic monitoring can be applied.Inotropic and vasopressor drugs should be administered through a central venous catheter via infusion pumps that can deliver precise flow rates. These agents are mostly short acting with rapid onset and offset of action. Therefore, they can be used without an initial bolus and can be titrated frequently. Abrupt discontinuation should be avoided because of possible hypotension.

Abstract

Objective. Multi-drug resistant bacterial infections, in particular when Methicillin-Resistant Staphylococcus Aureus (MRSA) is involved, have become a relevant problem in both general and specialized intensive care units. The aim of this study was to identify the epidemiology of MRSA infections in a Cardiac Surgical Intensive Care Unit, to assess their impact on mortality and to identify predictors of MRSA infection and mortality in this population.

Design and settings. A 7-year observational study in a cardiac surgery teaching center.

Participants. Eight thousand, one hundred and sixty-two microbiological samples were obtained from 7,313 patients who underwent cardiac surgery in the study period.

Interventions. None.

Variables of interest and main results. Twenty-eight patients (0.38%) had MRSA infection. The most frequent site of MRSA isolation was from bronchoalveolar samples. Hospital mortality was 50% in patients with MRSA infection and 2% in patients without MRSA infection (p<0.001).

Few preoperative independent predictors of MRSA infection and hospital mortality were found at multivariate analysis. Outcomes were found to be most influenced by perioperative variables. MRSA infection was the strongest predictor of mortality, with an odds ratio of 20.5 (95% CI 4.143-101.626).

Conclusions. Methicillin-resistant Staphylococcus aureus infections following cardiac surgery still have a strong impact on the patients’ outcome. More efforts should be directed toward the development of new risk analysis models that might implement health care practices and might become precious instruments for infection prevention and control.

Abstract

Objective. Sepsis is a complex inflammatory disease, rising in response to infection. Drotrecogin alfa, approved in 2001 for severe sepsis, has been withdrawn from the market. The aim of this study was to assess if drotrecogin alfa-activated can reduce mortality in the more severe septic patients.

Methods. We searched PubMed, Embase, Scopus, BioMedCentral, and in Clinicaltrials. gov databases to identify every randomized study performed on drotrecogin alfa-activated in any clinical setting in humans, without restrictions on dose or time of administration. Our primary end-point was mortality rate in high risk patients. Secondary endpoints were mortality in all patients, in patients with an Acute Physiology and Chronic Health Evaluation (APACHE) 2 score ≥ 25 and in those with an APACHE 2 score ≤25.

Results. Five trials were identified and included in the analysis. They randomized 3196 patients to drotrecogin alfa and 3111 to the control group. Drotrecogin alfa was associated with a reduction in mortality (99/263 [37.6%] vs 115/244 [47.1%], risk ratios (RR) = 0.80[0.65; 0.98], p = 0.03) in patients with multiple organ failure and a mortality risk in the control group of >40%, but not in the overall population or in lower risk populations.

Conclusions. In high risk populations of patients with multiple organ failure and a mortality of >40% in the control group, Drotrecogin alfa may still have a role as a lifesaving treatment. No beneficial effect in low risk patients was found. An individual patient meta-analysis including all randomized controlled trial on sepsis is warranted, along with new studies on similar drugs such as protein C zymogen.

Abstract

Endogenous protein C levels are frequently decreased in septic patients, probably due to increased conversion to activated protein C. Protein C levels inversely correlate with morbidity and mortality of septic patients regardless of age, infecting microorganisms, presence of shock, disseminated intravascular coagulation, degree of hypercoagulation, or severity of illness. Taken together, these considerations suggest a strong correlation between protein C pathways and survival from severe sepsis/septic shock, and reinforce the rationale for the attempts to normalize plasma activity of protein C to improve survival, hamper coagulopathy, and modulate inflammation. We therefore conducted a systematic review of all manuscripts describing protein C concentrates administration in adult and pediatric populations. We identified 28 studies, for a total of 340 patients, 70 of whom died (20.6%). Septic patients were the most represented in this review of case reports and case series. In the majority of these patients sepsis was associated with meningitis, purpura fulminans or disseminated intravascular coagulation. No bleeding complications related to the study drug were reported and most studies underlined normalization of inflammatory markers and of coagulation abnormalities. We conclude that protein C concentrate is an attractive option in septic patients (especially those with meningitis, purpura fulminans, or disseminated intravascular coagulation) and that its cost-benefit ratio must be studied with a large multicenter randomized control trial, possibly including also high risk patients with septic shock and multiple organ failure.

Abstract

Introduction. Fluid overload and a positive fluid balance are common in the intensive care unit (ICU). Furosemide is frequently administered to increase urine output. A bolus injection is the traditional mode of administration, but many concerns have been raised about possible intravascular volume fluctuations, toxicity and enhanced tolerance. Furosemide related adverse effects can be enhanced in critically ill patients. Continuous infusion should allow better hemodynamic stability, less side effects and an easier achievement of the desired diuretic effect. We performed a systematic review and meta-analysis to compare the effects and complications of continuous furosemide infusion with those of bolus injections in critically ill patients in the ICU.
Methods. Studies were searched in PubMed (updated January 2009). Backward snowballing of included papers was performed. International experts were contacted for further studies.
The inclusion criteria were: random allocation to treatment, comparison of furosemide bolus vs continuous infusion, performed in surgical or intensive care patients. The exclusion criteria were: non-parallel design randomized trials, duplicate publications, non-human experimental studies, no outcome data.
Results. Four eligible randomized clinical trials were identified, including 129 patients (64 to continuous infusion and 65 to bolus treatment). Continuous perfusion was not associated with a significant reduction in risk of mortality as compared to bolus injection
Conclusions. Furosemide in continuous perfusion was not associated with a significant reduction in risk of hospital mortality as compared to bolus administration in critically ill patients in ICU, but existing data are insufficient to confidently assess the best way to administer furosemide . Applying a protocol to drive furosemide therapy could be more relevant than the chosen mode of administration.